Thin-film thermoelectric cooling and heating devices for DNA genomic and proteomic chips, thermo-optical switching circuits, and IR tags

ABSTRACT

A thermoelectric cooling and heating device including a substrate, a plurality of thermoelectric elements arranged on one side of the substrate and configured to perform at least one of selective heating and cooling such that each thermoelectric element includes a thermoelectric material, a Peltier contact contacting the thermoelectric material and forming under electrical current flow at least one of a heated junction and a cooled junction, and electrodes configured to provide current through the thermoelectric material and the Peltier contact. As such, the thermoelectric cooling and heating device selectively biases the thermoelectric elements to provide on one side of the thermolectric device a grid of localized heated or cooled junctions.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority as a divisional of U.S. applicationSer. No. 10/118,236 entitled “Thin-film Thermoelectric Cooling AndHeating Devices For DNA Genomic And Proteomic Chips, Thermo-OpticalSwitching Circuits, And IR Tags,” filed Apr. 9, 2002, which claimspriority under 35 U.S.C. Sec. 119 to U.S. Provisional Application No.60/282,185 entitled “Thin-film Thermoelectric Cooling and HeatingDevices for DNA Genomic and Protemic Chips, Thermo-optical SwitchingCircuits, and IR Tags,” filed Apr. 9, 2001 The disclosures of U.S.application Ser. Nos. 10/118,236 and 60/282,185 are hereby incorporatedherein in their entirety by reference. This application includes subjectmatter related to that disclosed in U.S. Pat. No. 6,071,351; and U.S.Ser. No. 09/381,963, filed Mar. 31, 1997, entitled “Thin-filmThermoelectric Device and Fabrication Method of Same”; and U.S.Provisional Application Serial No. 60/190,924, filed March 2000,entitled “Cascade Thermoelectric Cooler”; and U.S. Ser. No. 60/253,743,filed Nov. 29, 2000, entitled “Spontaneous Emission Enhanced HeatTransport Method and Structure for Cooling, Sensing, and PowerGeneration”, the disclosures of which are hereby incorporated herein intheir entirety by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to thin-film thermoelectric cooling andheating devices for application in a broad range of applications fromDNA genomic and proteomic chips, thermo-optical switching circuits, andinfrared tags, and to the application of anisotropic heat spreaders toelectro-holographic optical switching, thermocapillary and bubblejetoptical switching, micro-strip delay lines for packet switching incellular communication, and temperature control for probes inmicro-surgery and bio-tissue analysis.

2. Description of the Background

Solid-state thermoelectric devices can improve the performance ofelectronic components, opto-electronic components and sensors. Today,thermoelectric devices based on bulk (about 1 mm thick)p-Bi_(x)Sb_(2-x)Te₃ and n-Bi₂Te_(3-x)Se_(x) alloyed materials are usedin cooling applications. FIG. 1A is a schematic of a bulk deviceconsisting of two thermoelectric materials 2 a, 2 b having anappropriate bias voltage for cooling at a Peltier contact 2 c. FIG. 1Bshows that the same device can be used for heating at the Peltiercontact with an appropriate opposite bias voltage. Bulk devices presenta cold surface or a hot surface existing across the entire top surfaceof the thermoelectric device. So far, bulk thermoelectric devices havenot been made to selectively heat or cool local regions without heatingor cooling adjacent areas because of their relatively large size (ofeach element) as well as lack of microelectronic type processing. Assuch, thermoelectric devices have not been employed in applicationsrequiring selective heating or cooling.

SUMMARY OF THE INVENTION

One object of this invention is to provide thin-film thermoelectricdevices that can cool or heat with response times of tens of μsecinstead of hundreds of msec for bulk devices, and another object of theinvention is to cool or heat extremely small areas, tens to hundred μm²,as compared to the mm² areas of bulk thermoelectric devices, are locallyheated or cooled.

Accordingly, one object of the present invention is to providespot-cooling and spot-heating at localized areas defined by the patternof thin-film thermoelectric devices and the applied electrical bias.

Another object of the present invention is to provide the spot heatingand/or cooling on the same side of a thermoelectric device.

Still another object of the present invention is to provide rapidheating or cooling to selective surface components.

Another object of the present invention is to provide a thin-filmthermoelectric device which can self-assemble DNA material for genomicand proteomic applications in a microarray format.

Another object of the present invention is to control reactionchemistry, through temperature control of reaction rates, betweenmolecules such as between DNA or between DNA and RNA or between proteinmolecules or between enzyme and reactants or in general between any twoor more molecules in an array format such as for example DNA-RNA,RNA-RNA, DNA-RNA, protein-DNA, protein-RNA, protein-ligand, andenzyme-substrate.

A further object of the present invention is to provide a thermoelectricdevice which can, via thermo-optical components, control opticalswitches in optical networks.

Another object of the present invention is to provide a thermoelectricdevice which can control the lasing frequency of a laser viatemperature-derived bandgap changes in the laser material.

Still another object of the present invention is to provide athermoelectric device which can perform spot cooling/heating to produceinfrared images for identity tags.

These and other objects of the present invention are achieved byproviding a thermoelectric cooling and heating device including asubstrate, a plurality of thermoelectric elements arranged on one sideof the substrate and configured to perform at least one of selectiveheating and cooling such that each thermoelectric element includes athermoelectric material, a Peltier contact contacting the thermoelectricmaterial and forming under electrical current flow at least one of aheated junction and a cooled junction, and electrodes configured toprovide current through the thermoelectric material and the Peltiercontact. As such, the thermoelectric cooling and heating deviceselectively biases each individual thermoelectric element to provide onone side of the thermolectric device a grid of localized heated orcooled junctions.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the U.S. Patent and TrademarkOffice upon request and payment of the necessary fee. A more completeappreciation of the present invention and many attendant advantagesthereof will be readily obtained as the same becomes better understoodby reference to the following detailed description when considered inconnection with the accompanying drawings, wherein:

FIG. 1A is a schematic illustration of a bulk thermoelectric device witha bias voltage for cooling a Peltier contact;

FIG. 1B is a schematic illustration of a bulk thermoelectric device withan opposite bias voltage for heating a Peltier contact;

FIG. 2A is an illustration of a spot cooled image in the form of “ONR”and “DARPA” as shown by the IR image, see temperature scale forreference;

FIG. 2B is another illustration of a spot heated image in the form of“ONR” and “DARPA” as shown by the IR image; see temperature scale forreference;

FIG. 3 is a schematic illustration of integrated spot-coolers forlocal-area cooling or heating;

FIG. 4 is an illustration of a combined spot cooling and spot heating ofa surface of a low thermal conductivity material header;

FIG. 5 depicts graphs illustrating the time responses of a 5 μmthin-film thermoelement as compared to a bulk (1 mm) thermoelement;

FIGS. 6A-6D are schematic illustrations of a single-strand of DNAproduced by selective electro-thermal spot-temperature control using thethin-film thermoelectric devices of the present invention;

FIG. 7A is a schematic illustration of a robotic deposition processutilized to deposit DNA material;

FIG. 7B is a schematic illustration of a self-assembly of DNA fragmentsor protein molecules obtained by selective temperature control using anelectro-thermal genomic chip or electro-thermal proteomic chip of thepresent invention;

FIG. 8 is an illustration of a spatially-controlled electro-thermalelectrophoretic DNA chip;

FIG. 9 is a schematic illustration of the attachment and unziping ofdouble-helical strands and the introduction of new DNA strand to behybridized, the strands being attached to an electro-thermal chip of thepresent invention illustrating spatial temperature control utilized forgenomics and proteomics study;

FIG. 10 is a flow chart illustrating multiple feedback processes betweenDNA, RNA, and proteins;

FIG. 11 is a schematic depiction of a thermoelectric probe of thepresent invention locally contacting a single cell of a specimen;

FIG. 12 is a schematic of a nano-scale thermal transducer of the presentinvention employing a cantilever arrangement contacting a single cell;

FIG. 13 is a schematic diagram depicting a nano scale thermal transducerof the present invention employing a cantilever arrangement contactingspecific spots of large molecular structures such as a hybridized DNApair;

FIG. 14 is a schematic depicting an apparatus of the present inventionfor detecting the heat released from a small-scale region;

FIG. 15 is a schematic depiction of a multiple wavelength VCSEL arraylocated on the thermoelectric device of the present invention; and

FIG. 16 is a schematic depiction of an elecrto-holographic routerswitching matrix located on the thermoelectric device of the presentinvention.

DESCRIPTION OF THE EMBODIMENTS

Referring now to the drawings, wherein like reference numerals designateidentical, or corresponding parts throughout the several views, and moreparticularly to FIG. 2A thereof, FIG. 2A is an illustration of a spotcooled image in the form of “ONR” and “DARPA” as shown by an IR imagefeature produced by cooling of the present thermoelectric devices. Insuch cooling, microelectronic lithography is employed to pattern microthermoelements arbitrarily across the surface of a substrate. The secondillustration in FIG. 2B shows an infra-red image generated by spotheating in a thermoelectronic device of the present invention. Theability to obtain spot cooling or heating with thin-film thermoelementsis enabled by the very low-resistivity specific contact resistivitiesleading to relatively high device (which includes the effect of contactresistance and that of the material) figure-of-merit (ZT>0.1 at 300K)which can be obtained with the thin-film thermoelements. By reversal ofthe bias voltage to the thermoelements, the spots can be made to heat asshown by the image of heated spots in FIG. 2B. Based on the results inFIGS. 2A and 2B, the device modules shown in FIGS. 3 and 4 can botharbitrarily cool and heat local surface spots.

FIG. 3 is a schematic of integrated spot-coolers for local-area coolingor heating. In FIG. 3, several thin-film thermoelectric elements areplaced in parallel and heat or cool a particular area depending on thedirection of current flow in these elements. As shown in FIG. 3, thethermoelectric cooling and heating device of the present inventionincludes a substrate 1 and a plurality of thermoelectric elements 2arranged on the substrate 1 with each thermoelectric element 2 having ann-type thermoelectric material 2 a, a p-type thermoelectric material 2 blocated adjacent to the n-type thermoelectric material 2 a, a Peltiercontact 2 c connecting the n-type thermoelectric material 2 a to thep-type thermoelectric material 2 b. Electrodes 3 contact both a side ofthe n-type thermoelectric material 2 a opposite the Peltier contact 2 cand a side of the p-type thermoelectric material 2 b opposite thePeltier contact 2 c.

Appropriately biased electrical current flow through selected ones ofthe thermoelectric elements 2 makes the Peltier contact 2 c either aheated junction 7 or a cooled junction 8. Further, the thermoelectriccooling and heating device of the present invention includes acontroller connected to the electrodes and configured to selectivelybias the electrodes of each of the thermoelectric elements in anappropriate direction to form the cooled junction or an oppositedirection to form the heated junction. As shown in FIG. 3, thethermoelectric elements 2 are patterned onto the substrate 1. Thispattern can frequently be a grid pattern, but many other patternsdesigned to interface the thermoelectric cooling and heating device ofthe present invention to specific applications are possible.

According to the present invention, a wiring grid can individuallyconnect to each of the thermoelectric elements providing the controlleraccess to each thermoelectric element for application of an appropriatebias for cooling or an opposite bias for heating. One side of all thethermoelectric elements can, according to the present invention beconnected to a common ground. Similar grid wiring connections andcontrol are utilized in liquid crystal display grids as described inU.S. Pat. No. 6,154,266, the entire contents of which are incorporatedherein by reference. However, the grids may alternatively be connectedor segmented in pre-designated sets (e.g. columns and rows) which arecommonly connected to have the same polarity of voltage simultaneouslyapplied, enabling the pre-designated sets to be block-addressed by thecontroller.

Contrary to FIG. 3, in one embodiment of the present invention, only oneleg of the thermoelectric element is required to produce heating orcooling. In this embodiment, a selected type of thermoelectric material(i.e. n-type or p-type) is utilized with the Peltier contact 2 c.Current flow in a first direction through an electrode, a thermoelectricmaterial, the Peltier contact 2 c, and a subsequent electrode results ina heated junction at the Peltier contact 2 c. A current flow in a seconddirection opposite to the first produces a cooled junction at thePeltier contact 2 c. Indeed, the spot cooled images in FIGS. 2A and 2Bwere produced utilizing current flow through an electrode, athermoelectric material, a Peltier contact, and a subsequent electrode.

FIG. 4 is an illustration of a combined spot cooling and spot heating ofa surface header 10 made of a low thermal conductivity material. Shownin FIG. 4 is an overlay chip 12 which mates to the surface header. Theability to both spot-cool and spot-heat on the same side of thethermoelectric device of the present invention permits flexibility inthe application of thermoelectric thin-film devices to temperaturedependent process control. In some applications, utilization of athermally insulating material (e.g. a low-thermal conductivity materiallike glass or quartz rather than a high-thermal conductivity materiallike AIN) for the heat-source header is not necessary to preserve thepattern of cooled or heated spots.

The thin film thermoelectronic devices of the present invention,according to one embodiment of the present invention, are thermallycoupled to a surface header 10 which is an anisotropic heat spreader inwhich the thermal conductivity is excellent in a direction normal to thesurface header (i.e. the direction of heat flow from a point which needsto be cooled or heated to the Peltier contact region of the device)while the lateral thermal conductivity in the plane of the surfaceheader (i.e. in a direction across the surface header 10) is low. Inthis embodiment, the anisotropic heat spreader includes a composite of ahigh thermal conductivity material (e.g., oriented crystals in apolycrystalline matrix or a high thermal conductivity rods (e.g.,silicon rods or copper rods) in a low-thermal conductivity matrix (e.g.,glass). The composite, according to the present invention, provides highthermal conductivity perpendicular to a plane of the surface header 10and low thermal conductivity parallel to the plane of the surface header10, thus preserving the spot-cooling/heating character of the thin filmthermoelectric devices of the present invention. Furthermore, theanisotropic heat spreaders, according to the present invention, canutilize other forms of-heat spreaders such as graphite or metal fibersin an aerogel matrix to achieve high thermal conductivity perpendicularto the plane of the header compared to low thermal conductivity in theplane of the header.

One advantage of the 1 to 10 μm thin-film thermoelectric devices of thepresent invention is that the spot cooling and/or spot heating isextremely fast. FIG. 5 illustrates the time-response of a 5 μm thickthermoelectric device and a time response of a typical state-of-the-artbulk (1 mm-thick) element after currents which produce cooling areapplied to these devices. As shown in FIG. 5, the thin filmthermoelectric device of the present invention responds within 15 μswhile the bulk thermoelectric device responds within 0.40 s. Thus, thethin-film thermoelectric devices of the present invention have a timeconstant on the order of a few microseconds, while the bulkthermoelectric devices have a time constant of hundreds of milliseconds.The time constant difference arise directly from the fact that thethermal response time (τ_(r)) is significantly smaller in thinnerthermoelements. The τ_(r) is approximately given by equation (1):τ_(r)=4L ²/² D   (1)

where L is thickness of the thermoelectric device and D is the thermaldiffusivity. Thus, the thin-film thermoelectric devices of the presentinvention have a fast response time allowing for rapid changes tosurface temperatures and hence rapid control of chemical, physical,mechanical, or optical phenomenon associate with these surfacetemperature changes. L for bulk thermoelectronic devices ranges from 500to 2000 microns in bulk while D ranges from 0.01 to 0.03 cm²/sec. Incontrast, L for thin-film devices ranges 1 to 10 microns while D inBi₂Te₃ superlattice thin-film materials is from 0.001 to 0.003 cm²/secand D in Si/Ge thin-film materials is from 0.01 to 0.05 cm²/sec. Higherspeed cooling/heating applications which require higher D and reasonableZT is needed to obtain cooling. For small temperature excursions, a lowZT can be sufficient. Thus, according to the present invention, higherspeed may be achievable with higher D materials such as for example InSband their alloys and PbTe and their alloys.

Further, the performance of any thermoelectric device is dependent onthe figure-of-merit (ZT) of the thermoelectric materials used tofabricate the device. The cooling or heating of the present inventioncan utilize high-performance high-ZT Bi₂Te₃-based superlatticestructured thin-film materials to obtain enhanced performance levels, asdescribed in U.S. patent application Ser. No. 09/381,963, the contentsof which have been incorporated herein by reference. Alternatively,non-superlattice structured thermoelectric materials can be used in thepresent invention. In general, the present invention is not limited toany particular design, material, or fabrication process of a bulk orthin film thermoelectric device.

Specific applications which can take advantage of the above describeddevelopments in small area/fast response time thin-film thermoelectricdevices include but are not limited to applications in DNA arrayfabrication, DNA electrophoresis for genome sequencing, DNA functionalgenomics, and DNA proteomics. Genomincs and protemics research have beendescribed in Proteomics in Genomeland, in Science, vol. 291, No. 5507,pp. 1221-1224, the entire contents of which are incorporated herein byreference. In addition, the thermoelectric devices of the presentinvention can be used for electro-thermal optical switching forhigh-speed optical communications and other selective-cooledoptoelectronic applications. Further, the thermoelectric cooling devicesof the present invention can be used as identification tags for militarypersonnel, military systems, and even commercial systems. Identificationtags utilizing the spot cooling or heating of the present invention canbe scanned by IR-imaging devices.

Fabrication of conventional DNA chips (or microarrays) forelectrophoresis or genomics or proteomics begins with glass siliconsubstrates. Onto these substrates are fixed or assembled thousands ofpatches of single-stranded DNA, referred to as probes. Each patchmeasures just tens of μm in lateral dimension. Microelectronicphotolithographic techniques offer the best technique for obtaining thehighest density of probes. Conventional production scale microarrays canhave 400,000 probes in 20-micron size patches. Conventional proceduresare described in Making Chips, in IEEE Spectrum, March 2001, pp. 54-60,the entire contents of which are incorporated herein by reference.

A first step in DNA analysis on a microarray fabrication is theseparation of twisted strands of the DNA by unzipping the DNA along therungs of the ladder, using temperature or biochemical methods. DNAconsists of nucleotides stacked atop each other in two strands forming atwisted ladder. The twisted ladder has the sugar-phosphate supportbackbone. The rungs of the ladder are the bases. Adenine pairings occurwith thymine, and guanine pairings occur with cytosine.

According to the present invention, the formation of single unzippedstrands of DNA molecules occurs using a spot-cooling/heatingelectro-thermal chip as shown in FIG. 6A. In the spot-cooling/heatingelectro-thermal chip of the present invention, patches are patternedlithographically in a receptacle array to have dimensions ranging from 1to 500 m. FIGS. 6A-D show schematically the steps of forming asingle-strand of DNA by selective electro-thermal spot-temperaturecontrol. A template 11 is attached to the surface header 10 where theDNA array is to be located. The DNA double helix will typically unzip atthe “hot” points. However, certain DNA molecules, depending on theirchemistry, may selectively unzip at “cold” points. Thespot-cooling/heating of the electro-thermal chip of the presentinvention will heat or cool the DNA to predetermined temperatures tounzip the DNA strands, as shown in FIG. 6B. Once the DNA strands areunzipped at the respective “hot” or “cold” locations, theelectro-thermal chip of the present invention can by charge control(using the fact that DNA molecules themselves carry charge) adhere DNAto predetermined areas on the surfaces of the electro-thermal chip.Alternatively, selective cooling can be utilized to enhance adsorptionof a single strand of DNA to a specific site. Thus, the electro-thermalchip of the present invention produces single-strand generation andselective adsorption at predetermined locations. These steps, accordingto the present invention, can be followed by attachment andsingle-strand generation of another DNA molecule at adjacent locations,as shown in FIG. 6C. In FIG. 6D, the process of selective adsorption ofvarious DNA molecules at the all desired sites is complete. Thus, onceself-assembled, the DNA array is available for analyticalcharacterizations such as for example mass spectroscopic analysis, NMRstudies, x-ray analysis, etc.

DNA microarrays numbering 100,000 to a million, with 20-micron sizepatches, can typically be deposited on glass or silicon substrates byrobotic deposition as shown in FIG. 7A. However, robotic deposition istime consuming and costly. Conventional robotic deposition techniqueshave been described in U.S. Pat. No. 5,865,975, the entire contents ofwhich are incorporated herein by reference. Instead, according to thepresent invention, by using a electro-thermal cooling/heating chip asshown in FIG. 7B, spot temperature control will self-assemble selectiveDNA or proteins. FIG. 7B is a schematic of a self-assembly of DNAfragments or protein molecules obtained by selective temperature controlusing an electro-thermal chip of the present invention. Thus, rapidfabrication of pre-determined DNA arrays for genomics or protein arraysfor proteomic studies is realized by the self-assembling character ofthe biological material when deposited on the electro-thermal genomic orproteomic chips of the present invention.

Further, the spatially-controlled-temperature of the thin-filmthermoelectric devices of the present invention can be utilized withexisting DNA array fabrication methods. Today, DNA arrays are madeeither by inkjet printing or by in-situ fabrication. The inkjet printingprocess has been described in U.S. Pat. No. 6,180,351, the entirecontents of which are incorporated herein by reference. In the inkjetprinting process, droplets containing many copies of a sequence of DNAare deposited on a substrate. The thin-film thermoelectric device of thepresent invention permits spatial temperature control combined withrapid cooling/heating to promote adhesion or adsorption of the DNAstrands. Furthermore, the in-situ fabrication of DNA sequences by thephotolithography process, as described in U.S. Pat. No. 5,874,219, theentire contents of which are incorporated herein by reference, can bereplaced by the selective adhesion of the DNA at the spot-temperaturecontrolled areas on the thin-film thermoelectric device of the presentinvention. For example, the traditional in-situ fabrication of DNAsequence by deposition of one nucleotide at a time(shown in FIG. 7 a.)can be replaced by thermal activation or cooling-enhanced adsorption ona spatially-controlled-temperature grid. Thus, the self-assembly methodof the present invention avoids exposure of the DNA to UV light requiredin the traditional photolithographic process. UV exposure can causeunintentional chemical modification of the DNA. Further, replacing spotphoto-chemistry with spot thermochemistry of the present invention hasother advantages in that the DNA is preserved in tact without chemicalmodification, as can occur when the capping chemicals used in thetraditional photolithographic DNA array process are applied.

In addition to spot temperature control, in another embodiment of thepresent invention, spot temperature control can be combined spotelectric fields. For example, arrays of electrically active (−1.3 to22.0 Volts) pads can, according to the present invention, control thepooling of DNA onto particular sites. Pooling of DNA onto electricallycharged sites speeds the hybridization reaction of the DNA by a factorof as much as 1000. Hybridization represent the pairing of individualgenetic species which belong to genetically different species. Forexample, complementary RNA and DNA strands can be paired to make aRNA-DNA hybrid which forms a “new” double-strand from geneticallydifferent sources. FIG. 9A is a schematic illustration of DNA strandseach containing a double helix, separation of the strands, and theintroduction of new DNA strand to be hybridized. FIG. 9B is a schematicillustration of an electro-thermal chip of the present invention whichdepicts spatial temperature control utilized for genomics and proteomicsstudy. Formation of new pairs can be assisted in the present inventionby cooling weakly hybridized pairs to inhibit the strands fromprematurely breaking apart before hybridization. Furthermore, excessivetemperatures can result in a hybridized pair dehybridizing, defeatingthe engineering process.

Thus, the process of selective adsorption, single-strand generation, andhybridization as directed by the thin-film thermoelectric devices of thepresent invention is accomplished by decreasing the temperature atselected sites to facilitate charge-bonding or electrovalent bonding ofa first set of DNA strands to lysine which pre-existed on a template ofthe selected sites, exposing the charge-bonded or theelectrovalent-bonded DNA strands to UV light to cross-link the lysineand the DNA strands, heating the selected sites to unravel the first setof DNA strands whereby one strand is no longer attached, introducing asecond set of DNA strands, and hybridizing the second set of DNA strandsto the attached single stranded DNA of the first set.

Further, the present invention provides a tool by which chemical kineticprocesses of DNA cell systems can be studied to observe reaction ratesaffected not only by temperature but also by other physical and chemicalparameters. Currently, genomic data is static: sequence and structure.Dynamic information in the form of enzymology experiments, which measurereaction kinetics in DNA microchips and arrays, would yield valuableinformation. The reaction kinetics studied in conventional DNAmicroarrays suggest that study of faster chemical reaction times throughspatial temperature control can lead to a better understanding and couldeventually permit manipulation and control of DNA reaction kinetics.Genomic engineers need to reduce the experimental iterations to betterunderstand the DNA structure and need faster analysis when introducingdeliberate changes to the functional genomics. Control of the DNAstructure will profoundly influence the speed and ability to safelyengineer new crops, medicines, and genetic treatments. According to thepresent invention, the thermoelectric elements can act as localizedthermo-genetic switches to switch (i.e. temperature activate) DNAchemistry, DNA-RNA chemistry, protein synthesis, enzyme-aidingconversion of dominant genes to recessive genes and vice-versa, andproduction of medical antibodies.

Furthermore, interpreting data from DNA micro-arrays has emerged as amajor difficulty. An array is a technology that provides massivelyparallel molecular genetic information. Biostatistics and bioinformaticswhich truncate the data defeat the whole purpose of array sampling.Usually, the data in such arrays are interpreted by finding a logicallink between the expression of a gene and its function. Since biologicaland chemical processes are controlled by temperature, temperaturecontrol in micro-arrays as enabled by the present invention will act asa control lever. Raising the temperature will accelerate reactions;lowering the temperature will retard reactions. Statistically ManageableA real Rapid Temperature-control DNA arrays or SMART DNA arrays can bedeveloped using the thermoelectronic devices of the present invention toaid in data interpretation, particularly the finding of functionallinks.

Advantages of the spot-cooling/heating method of the present inventioninclude (1) high-speed inkjet printing of DNA micro-arrays using spatialtemperature-controlled thin-film thermoelectric devices to assistself-assembly, (2) replacement or augmentation of photolith-based DNAmicro-arrays with thermochemistry using the spatialtemperature-controlled to form the array of DNA, (3) rapid thermalcycling for DNA sequencing, and (4) DNA sequencing for high throughputprocess for determining the ordered base pairs in DNA strands.

Another embodiment of the present invention, aspatially-controlled-temperature electro-thermal electrophoretic chip,as shown in FIG. 8. For clarity, only a few cooling and heating spotsare shown in FIG. 8. Yet, a large number of electrophoretic array spotsexist in the electrophoretic chip. Spot sizes of the present inventionranging from 5 μm*5 μm to 1000 μm*1000 μm, resulting in spot densitiesranging from 100 to a million or more spots per cm². The electro-thermalelectrophoretic chip of the present invention cools hot spots generatedduring electrophoresis of DNA. For example, the heat generated duringelectrophoresis can approach 30 to 100 W/cm². Removal of such high heatfluxes can be easily achieved with microelectronically processedthin-film thermoelectric devices (see for example U.S. patentapplication Ser. No. 09/381,963). Further, in electrophoresis, theability to individually cool or heat in a controlled 20 μm*20 μm patchor other similar geometries provides a tool to understand, modify, andcontrol DNA electrophoresis. In addition, charge control can beaugmented to provide selective adsorption at precharged sites.

The method of choice for DNA sequencing to determining a size of a DNAstrands is a four-color electrophoresis utilizing fluorescent labelingspecific to the bases in the DNA. There are several sources of noise insuch analysis such as surplus DNA without attached fluorescent labels,single-stranded DNA folding on itself, etc. These noise sources arereduced using purification of samples before loading, engineering of geland buffer chemistries and optimization of temperature, all leading tobetter resolution. The spatially-controlled-temperature electro-thermalelectrophoretic chip can potentially solve several of these problemsleading to faster and reliable DNA sequencing. For example, it is knownthat if the temperature is sub-optimal, the folding of the single strandof DNA can change the electropherogram. Thus, by using thespatially-controlled-temperature electro-thermal electrophoretic chip ofthe present invention, in one process step, the optimal temperaturerange can be obtained leading to faster DNA sequencing.

Another embodiment of the present invention is aspatially-controlled-temperature electro-thermal chip for self-assemblyof biological material. Today, DNA microarrays or biological chips aremade as follows. Using polymerase chain reaction or biochemicalsynthesis, strands of DNA are separated. Photolithography techniques areused to convert glass, plastic, or silicon substrates into a receptaclearray for DNA strands. Electrophoretic bonding or robotic deposition ortiny droplet sprayers are used to adhere the genetic material to thesubstrate. With the present invention, the receptacle array is thermallycoupled to a spot-cooling/heating thin-film thermoelectric module torealize the electro-thermal chip of the present invention. DNA strandscan be self-assembled by the spot-temperature control processillustrated in FIGS. 6 and 7. The spot-cooling/heating thin-filmthermoelectric module in the electro-thermal chip is reusable fromreceptacle to receptacle. Thus, the electrothermal chip of the presentinvention permits rapid self-assembly of DNA arrays and reduces the costof fabrication of DNA chips by avoiding robotic or photolithographic DNAtransfer techniques. The electro-thermal chip of the present inventioncools or heats very small areas, such as 20 μm*20 μm spots as in the DNApatches of a modem microarray. Thus, each of the 20 μm*20 μm patches orother similar geometries, if individually cooled or heated in acontrolled manner, provides a tool to understand, modify, and controlDNA genomics.

Proteins are chains of amino acids assembled in an order specified bythe sequence of DNA bases located in the chromosomes in the cellnucleus. RNA molecules move messages from the nucleus to ribosomes thatassemble proteins by matching three-base sets (codons) in message-RNAwith complementary codons on transfer RNA attached to individual aminoacids. This orderly sequence relates the “expression” of gene to“activity” of protein in the cell. However, this relation is verycomplicated with multiple feedback loops as shown in FIG. 10.

As a result of the modifications from regulations and feedback, somecomplex human genes can produce hundreds of different proteins. Toolsare needed to do a high-throughput study of the non-genome (feedbacks)interactions shown in FIG. 10. Unlike genomics, there is no microarrayfor measuring the concentration of many proteins simultaneously. Today,the only way is to separate different proteins is by mass, sincedifferent amino acids sequences correspond to different masses. Thepresent invention utilizes 2-D gel electrophoresis which is similar tothe electrophoresis used in DNA sequencing such that disclosed in Fitchand Sokhansanj, Proc. of IEEE, December 2000, the entire contents ofwhich are incorporated herein by reference. An electric field is appliedalong one axis to get a 2-D spot representing the concentration of aparticular protein in the sample. Spot-cooling or spot-heating in atwo-dimensional array, utilizing the electro-thermal chip of the presentinvention, offers a new approach to the study of proteomic chips.Further, electric field variations can be combined with temperaturevariations to manipulate the protein formation in simulation of realconditions.

For example, the temperature variations in the electro-thermal chips canbe used as a genetic switch to control or regulate the pathway of genesin how they synthesize proteins. The fast response time/small areacontrol in a electro-thermal chip will provide a control system toproduce useful proteins in an orderly fashion. Thus the fast responsetime/small area control, in combination with the electric field control,afforded by the electro-thermal chip of the present invention can leadto the implementation of stable regulatory pathways for proteinsynthesis from gene expressions. Further, synthesis, characterization,and manipulation of heat shock proteins (and the related DNA) in amicro-array utilizing the electro-thermal chip of the present invention,is enabled by the ability to rapidly change the temperature. There areabout 23 genes, out of a total of about 1367 typically concerned withhuman toxicology, that are classified as specific to heat shockproteins.

Temperature selection using spatially-temperature-controlledelectro-thermal chips can be used to control either the production ofmRNA, the transport of mRNA and the translation of mRNA to protein, allleading to new applications in new crops, medicines, and genetictreatments. For example, the reaction rate constants that control thebinding of RNA polymerase with DNA can be controlled with temperature sothat the effects of repressors can be overcome and so new proteins(enzymes) can be generated. Similarly, temperature can be controlled toprovide a sharp burst of mRNA to generate proteins.

Thus, a further embodiment of the present invention is aspatially-controlled-temperature electro-thermal chip for proteomicstudies. As previously noted, the electro-thermal chip of the presentinvention cools or heats very small areas, such as 20 μm*20 μm spots asin the DNA protein patches of a modern microarray. Thus, each of these20 μm*20 μm patches and other similar geometries, if individually cooledor heated in a controlled manner, will provide a tool to understand,modify, and control proteomics.

The effect of temperature control on DNA analysis, DNA amplification,protein synthesis, and DNA chemistry has been unstudied in DNAmicroarrays mainly because of the lack of suitable chip technologies.There are some studies that indicate that temperature may havesignificant importance in DNA analysis, DNA amplification, and generalDNA and protein chemistry. For example, in the DNA study of Yersiniapestis, the virulence mechanism of Yersinia pestis become active at 37C. J. P. Fitch and B. Sokhansanj, in Proc. of IEEE, Vol. 88, No. 12, pp.1949-1971, (2000), the entire contents of which are incorporated hereinby reference, have shown that some Yersinia pestis genes are expressedmore at 37 C than 25 C while others are expressed more at 25 C than at37 C. Temperature control studies can be accomplished in one step usinga spatially-temperature-controlled electro-thermal chip of the presentinvention. Rapid heating of small volumes using IR radiation has beenutilized in DNA amplification in polymerase chain reaction (PCR), seefor example IR-Mediated PCR,http://faculty.virginia.edu/landers/project.htm, the entire contents ofwhich are incorporated herein by reference. IR-mediated heating has alsobeen studied in enzyme assays.

Thus, in another embodiment of the present invention, an electro-thermalPCR chip of the present invention is utilized to locally heat or coolDNA sample. The electro-thermal PCR chip can control the temperaturemore locally than techniques which rely on volumetric heatingtechniques, e.g. IR radiant heating. In one embodiment of the presentinvention, the electro-thermal PCR chip replaces photochemistry withlocalized thermochemistry.

As previously noted, some Yersinia pestis genes were expressed more at37.degree. C. than 25.degree. C. while other genes expressed more at25.degree. C. than at 37.degree. C. A gene is expressed when the geneacts as a site to make a distinctive protein, leading to a biologicalactivity like virulence. DNA microarrays have been powerful templatesfor understanding patterns of gene expressions. Similarly, the strengthof a gene's expression depends on how much of the distinctive proteinsare made. Thus, weak genes may be transformed into strong genes, bylocal thermochemistry control. Temperature control for gene expressionstudies can be easily accomplished in one step using thespatially-temperature-controlled electro-thermal genomic hip of thepresent invention.

Along the same lines, it may be possible to convert with temperaturecontrol native genes of an individual that would normally not be able tofight certain bacterial infections to genes which can be chemicallyalert, thus resistant to bacterial infections. Once the converted genehas been expressed, the subsequent antibodies, i.e. the byproducts ofthe electro-thermal chip, can be “safely” transferred to the individual.

While conventional DNA microarrays are relatively easy to fabricate, asignificant problem with many DNA array experiments is that thehybridization is not perfect. This in turn necessitates redundancy andthus reduces speed. Spatial temperature control utilizingelectro-thermal genomic chip represents an expedient way to find optimaltemperatures to achieve improved hybridization. According to the presentinvention, electro-thermal heating/cooling can be integrated withmicrochips to perform PCR on substrates such as glass which normallyinhibit hybridization reactions. The fast response times associated withthe present thin-film thermoelectric devices are advantageous for rapidand effective thermocycling of PCR mixtures.

The electro-thermal electrophoretic chip, electro-thermal PCR chip, andthe electro-thermal chip of the present invention are compatible withthe low-thermal conductivity silica, glass sides or nylon membranes. Aselectrical insulators, these materials integrate spot temperaturecontrol and electrical charge control.

Also, the production of high-quality protein crystals necessary fordetailed characterization has been difficult.Spatially-temperature-controlled electro-thermal proteomic chips of thepresent invention can be used to crystallize protein crystals byoptimizing the temperature. A single chemistry process sequence, withspatially varying temperatures, can produce a whole range of crystalswhich in turn can be characterized. Structural genomics is an effort todo high-throughput identification of the 3-D protein structurescorresponding to every gene in the genome. There are two experimentalmethods for determining 3-D protein structure: NMR and X-raydiffraction. NMR measures the coupling of atoms across chemical bondsand short distances through space under the influence of a magneticfield. A variable temperature NMR analysis, of the same protein, locatedat various points of a spatially-resolved electro-thermal chip of thepresent invention can offer new insights into structural identification.Similarly, variable temperature X-ray crystallography of the sameprotein can be done to understand structures of various proteincrystals.

In a further embodiment of the present invention, the thermoelectricdevices of the present invention are utilized in electrophoresisapplications in an array format for single-stranded conformationpolymorphism (SSCP) detection. Mass spectroscopy studies of DNA sequencepolymorphisms as well as PCR processes have been described in U.S. Pat.No. 5,869,242, the entire contents of which are incorporated herein byreference. Additionally, it has been found that temperature control isparticularly crucial in applications such as SSCP where precisetemperature selection allow detection of mutations which are apparentonly at specific temperatures. Typically these temperatures can rangefrom near 0 to 80 C, with 1 C control. By thermally coupling thethermoelectric devices of the present invention to the SSCP array,precise temperature control is achieved.

In another embodiment of the present invention, the thermoelectricdevices of the present invention are utilized for precise temperaturecontrol in probes and prosthetics used for micro-surgery andbio-tissues. Rapid and spot temperature control, both in heating orcooling mode, is particularly useful in medical applications such as inmicro-surgery involving bio-tissues as in brain tissues. Spottemperature control, especially in the cooling mode without a lot ofheat dissipation, using the high-performance thermoelectric devices ofthe present invention would control the temperatures of bio-tissues on achronic basis for providing relief against variety of ailments such asfor example, epilepsy seizures from certain regions of the brain.According to the present invention, high-performance thermoelectricdevices based on high-performance materials, such as superlattices,leads to longer battery life in such chronic applications and reducedparasitic heat dissipation in nearby tissues.

Besides biological applications, in another embodiment of the presentinvention, the fast response time/small area thin-film thermoelectricdevices can be used for electro-thermal optical switching forhigh-speed, high-density optical communication networks as well as for avariety of selective (individual component controlled) cooling orheating in integrated optoelectronic transmitters/receivers.

For example, space-division optical switches are utilized in optical tomake fiber-to-fiber interconnections. For large-scale optical networks,a planar technology for switching is preferred. Mechanical switches,employing mechanical moving elements such asmicro-electro-mechanical-system (MEMS) mirrors or magnets, are notscaleable to large-scale M*N switches. In addition, repeatability,wear-and-tear and reproducibility of moving elements in MEMS mirrors aswell as the requirement of high voltages (about 50 Volts) for operationare undesirable features.

Waveguide space-division switches can realize large-scale N*N switches.Typically, the switching function is achieved by controlling therefractive indices of the waveguide elements. The physical mechanismused to control the refractive indices of these waveguides depend on thewaveguide material. Silica planar waveguide type switches typicallyemploy an electrode that changes the temperature of a waveguide by athermo-optic effect. Thermo-optic devices are described in U.S. Pat. No.6,084,050, the entire contents of which are incorporated by reference.Other waveguide switches include semiconductor waveguide switchescontrolled by current injection, and ferroelectric crystal(LiNbO₃)-based switches, controlled by an applied electric field.Although semiconductor-based switches and LiNbO₃-based switches canachieve high switching speeds (switching time about 10⁻⁹ sec), it isdifficult to realize polarization independent switches with thesetechnologies.

Silica planar waveguide switches employ a Mach-Zender typeinterferometer as basic switching elements. For example, a thermo-opticphase-shifter in an interferometer changes the propagation delay in theinterferometer. Although the response time of conventional thermo-opticswitches is of the order of a ms, thermo-optic switches offer manyadvantages such as polarization independence and stability againstenvironmental changes. By combining thermo-optic switches into a 2*2array, a large scale matrix optical switch can be realized, as long asthe switch elements are loss-free and 100% of the input power istransferred to desired output ports. However, in real switchingelements, several problems arise including loss imbalance among theoutput ports and cross-talk. Typically, dummy switches are employed forovercoming such effects.

According to the present invention, Mach-Zender interferometer switchescan utilize the fast response time/small area thin-film thermoelectricdevices of the present invention to change propagation delays.Thermoelectrically heated/cooled thin-film thermoelements are attached,according to the present invention, to silica waveguides to obtain thenecessary switching function. The waveguide switches can becross-connected waveguides. Each section of the waveguide can be heatedor cooled so as to change the refractive index, affecting the opticalpathlength, and thus determining whether constructive or destructiveinterference occurs. The thin-film thermoelectric elements of thepresent invention can switch in tens of μs (see FIG. 5) or even smaller.Two to three orders of improvement in speed with electro-thermalMach-Zender optical switches coupled to the thermoelectric coolers ofthe present invention are expected as compared to conventionalthermo-optical switches. For example, the reversibility of temperature(with reversal of current) with thin-film thermoelectric devices of thepresent invention can be used advantageously in a “quenching” mode tofurther increase the speed of a waveguide switching element of thepresent invention.

Furthermore, simultaneous heating (in one interferometer leg) andcooling (in the other interferometer leg) will, according to the presentinvention, enhance the differential gain in the switching efficiency.These dual-temperature electro-thermal Mach-Zender optical switches willconsiderably reduce the number of dummy switches typically employed.This reduction leads to reduced losses and therefore a reduced need forperiodic fiber amplification.

The thin-film fast response time/small area thermoelectriccooling/heating devices of the present invention can be combined withpolymeric optical waveguide switches as well. Fluorinated polymers havelarge thermo-optic coefficients. The combination of such largecoefficients with the ability to obtain both heating and cooling withthin-film thermoelectric devices can, according to the presentinvention, produce low-loss, large, planar switching networks. Thin-filmthermoelectrically controlled thermo-optical switches can be operated aselectro-thermal optical switching networks, offering advantages such aslow insertion loss, polarization insensitive operation, long-termsolid-state reliability, and suitability for large-scale integration.

Large scale switches require large refractive index changes at theswitching element. This requirement means that temperature excursionsbeyond the average room temperature excursions must be realized before aswitching phenomena can be distinguished from noise due to roomtemperature variations. Heating, as in conventional thermo-opticswitches, is not an attractive way to implement such large temperatureexcursions since large heating temperatures are not desirable for othercomponents in the integrated optical system. However, a combination ofcooling and heating, simultaneously, can achieve larger temperaturedifferentials. For example, with a thermo-optic coefficient of dn/dT ofabout 1e-4 K⁻¹, as in the polymeric waveguides, approximately 75 C ofheating (implying about 100 C hot point if room temperature is 25 C) isnecessary to obtain 0.75% refractive index difference waveguides (i.e.0.75%-D waveguide). This 0.75%-D waveguides can be used for a 8*8switching matrix. For about the same reliability and performance-loss, a16*16 matrix with a 1.5%-D waveguides is necessary. This would imply,for a dn/dT of about 1e-4 K⁻¹, a hot point of 175 C with a referencepoint of 25 C. However, if simultaneous heating and cooling were used tocreate a large temperature differentials, a lower “hot” points would berealized. For example, for a 0.75%-D waveguide with a 50 C hot point and-25 C cold point could be employed using the anywhere anytimethermoelectric cooling/heating devices of the present invention.Similarly, for a 1.5%-D waveguide, a 100 C hot point and -50 C coldpoint could be employed using the anywhere anytime thermoelectriccooling/heating devices of the present invention. A greater than 1.5%-Dwaveguides can be realize utilizing a combination cooling/heatingthermoelectric device to create at least a 16*16 switching matrix. Theuse of “lower” absolute hot temperatures, for the same inducedrefractive index change, avoids high-temperature deterioration ofpolymeric materials, thus opening up the range of electro-opticmaterials which can be used in this application.

In another embodiment the fast response time/small area thermoelectriccooling/heating thin-film technology of the present invention is appliedto optoelectronic circuitry. One technology enabler for all-opticalnetworking is a component known as a multi-wavelength substrate.Otherwise, extensive wavelength-selective routing and add/dropcapabilities are needed to provide rigid capabilities and thus costlyimplementations.

The ability to design and deploy an optical network layer hierarchy hasbeen limited by the conventional process in which all lasers on a waferhave the same emission wavelength and lasing characteristics. Oneapproach is to manufacture on a single wafer diode lasers (e.g.distributed feedback DFB lasers) with different emission wavelengthswithin a gain bandwidth of 1530 nm to 1560 nm of the erbium doped fiberamplifier, and to control the grating pitch to increments of less than0.01 nm. The control of the grating pitch can be enormously relaxed,leading to greater device yields, if temperature variations (usingelectro-thermal spot cooling/heating control) is combined with gratingcontrol. Temperature variations change the bandgap of the lasingsemiconductor material in the active region of the laser, which in turncontrols the lasing wavelength. For example, 30K heating or cooling fromambient can change the wavelength by about 15 nm. Thus, a change from30K cooling to 30K heating, will produce a 30 nm wavelength shift. Thus,a multi-wavelength hybrid electro-thermal-spot-temperature-controlledDFB lasers for multi-wavelengths laser applications is realized by thepresent invention and permits active wavelength shifting.

Vertical-cavity surface-emitting lasers (VCSELs) are well suited foroptoelectronic applications due to the fact that the well-confirmedcircular surface emission is compatible with easy/efficient coupling tooptical fibers as well as that the devices can be pre-tested at thewafer level before packaging. VCSEL and VCSEL-based devices aredescribed in U.S. Pat. No. 6,154,479, the entire contents of which areincorporated herein by reference. VCSELs are compatible with wafer-scalemanufacturing. Here again, electro-thermal spot cooling/heating controlcan be employed to thereby control the bandgap of the active lasingmaterial, to produce multiple wavelengths. Thus, multiple wavelengthelectro-thermal spot-temperature-controlled lasers are realized by themulti-wavelength electro-thermal-spot-temperature-controlled VCSELs ofthe present invention. Large-area VECSEL devices are about 0.01 to 0.02cm². Spot cooling of such devices can be accommodated by thethermoelectronic devices of the present invention.

Another technology enabler for all-optical networking is the ability towavelength translate for payload transparency demanded by carriers onoptical networks. The multi-wavelength hybridelectro-thermal-spot-temperature-controlled DFB lasers and themulti-wavelength electro-thermal-spot-temperature-controlled VCSELs ofthe present invention will, along with the electro-thermal spotheating/cooling of Mach-Zender optical switches, attenuators, andfilters enable flexibility in wavelength operation and wavelengthshifting operations. The integration of optical components including DFBlasers into optical switching networks have been described in U.S. Pat.No. 6,072,925, the entire contents of which are incorporated herein byreference.

In another embodiment of the present invention, the thermoelectricdevices of the present invention are thermally in contact withthermocapillary optical switches enabling operation of high-speedthermocapillary switches. Thermocapillary switches seal fluid with abubble in a slit. Thermocapillary and bubble switches have beendescribed in U.S. Pat. No. 6,062,681, the entire contents of which areincorporated herein by reference. Typically heaters at either end of theslit shift the bubble in the fluid from side to side away from the heatsource to manipulate the optical path, thus achieving an optical gate.By replacing the passive micro-heaters with the active thermoelectricdevices of the present invention (which can be reversibly cooled byswitching the current direction), the switching speed is enhanced. Theaugmentation of such a slit with spot cooling and the fast responsethermoelectric devices of the present invention enhances the switchingefficiency, leading to lower optical loss. Thus, high speedthermocapillary switches can utilize a higher number of ports than whatis available today with the same optical loss. With reduced opticalloss, the high-speed thermocapillary switches of the present inventionare applicable to be used other than just as protection switches whichroute traffic around network disruptions.

In another embodiment of the present invention, the thermoelectricdevices of the present invention are thermally in contact with bubblejetoptical switches, thus enabling operation of high-speed bubblejetswitches. Bubblejet switches involve a small hole at each intersectionof a waveguide, filled with a fluid that has an index of refractionidentical to that of the waveguide. Consequently, light traverses eachintersection as though no trench was there. However, by micro-heatingthe fluid, a small bubble forms in the intersection and diverts opticalsignals down another path. By replacing the passive micro-heaters withthe active thermoelectric devices of the present invention (which can bereversibly cooled by switching the current direction), the switchingspeed is enhanced. The augmentation of such a waveguide suitably withspot cooling and heating can enhance the switching efficiency, leadingto less optical loss.

In a further embodiment, a 3-substrate sandwich which monolithicallyintegrates a “middle-wafer” VCSEL chip with electro-thermal spotcooling/heating thin-film thermoelectric chip on one side for wavelengthselection/control and another electro-thermal spot cooling/heatingthin-film thermoelectric chip on the other side for directionalcoupling/switching/attenuation functions can be realized by the presentinvention.

In still another embodiment, the electro-thermal spot cooling/heatingthermoelectric technology of the present invention can, according to thepresent invention be integrated with optoelectronic modules. Forexample, a typical VCSEL-based transceiver module has a bias circuit,laser driver, monitor diodes, VCSEL arrays, out-going opticalconnectors, in-coming optical connectors, photodetectors,pre-amplification circuits, and post-amplification circuits. Usingelectro-thermal spot cooling/heating chip of the present invention, itis possible to individually optimize the performance of many of thesecomponents on a chip.

In another embodiment of the present invention, high-speed spottemperature control of the thermoelectric devices of the presentinvention is thermally coupled to an electroholographic optical switch.The electroholographic optical switch, according to the presentinvention, can include Potassium Lithium Tantalate Niobate (KLTN)crystals in packet-switching optical networks. Typically, KLTN crystalshave dimensions of about 2 mm*2 mm*1.5 mm. Conventional bulkthermoelectric technology is not well suited to achieve cooling in suchsmall crystals. R. Hofineister et. al., Physical Review Letters, vol.69, pp. 1459-1462, (1992), the entire contents of which are hereinincorporated by reference, have shown that KLTN crystals can be cooledto temperatures around −23 C to enhance the quadratic electro-opticeffect, the basis for electroholographic optical switching. Thequadratic electro-optic effect dramatically increases as aferroelectric-paraelectric transition temperature of −23 C isapproached. Cooling of KLTN crystals to achieve higher diffractionefficiency or electro-optic efficiency in electroholographic opticalswitches can reduce the need for large voltages in switching networks.For example, in KLTN crystals, for the same quadratic electro-opticeffect leading to a diffraction efficiency of 5%, an electric field ofnearly 1500 V/cm is required at 21 C whereas an electric field of only250 V/cm at −15 C. Thus, for a given crystal of thickness 1.5 mm, the DCvoltage needed to provide the electric field would drop from around 225V to approximately 38V. According to the present invention, spot-coolingKLTN crystals, with areas such as for example of a 0.1 mm*0.1 mm size,allows smaller voltages to be used for producing the requisite electricfield. Smaller voltages are attractive from a system implementationpoint-of-view.

Furthermore, thermal expansion effects complicate the storage of volumeholograms, stored as spatial distributions of space charge. Temperaturestabilization of KLTN crystals in electroholographic optical switchesthe thermoelectric cooling technology of the present invention enableshigh-resolution (i.e., the smallest) spacing of the various wavelengthsthat are switched by the KLTN crystals. The higher the resolution ofthis spacing, the larger the number of wavelengths that can be preciselyswitched in dense wavelength division multiplexing (DWDM) networks.Similarly, according to the present invention, temperature control isutilized to vary a spatial distribution of space charge, thereby tuningthe holographic grating to a particular wavelength. Thus, the samephysical grating, with variable temperature control offered by thethermoelectric cooling technology of the present invention, allowswavelength translation needed for payload transparency in DWDM opticalnetworks. FIG. 15 is a schematic depiction of a multiple wavelengthVCSEL array 1502 located on a thermoelectric device 1504 of the presentinvention. FIG. 16 is a schematic depiction of an elecrto-holographicrouter switching matrix 1602 located on the thermoelectric device 1604of the present invention.

In yet a further embodiment of the present invention, the smallarea/fast response time of the thermoelectric devices of the presentinvention are utilized to control other electro-optic crystals operatingin the paraelectric regime.

In another embodiment of the present invention, the small area/fastresponse time of the thermoelectric devices of the present invention areutilized in an electronics module to selectively cool or control thetemperature of discrete module components, such as for example diodes,capacitors, inductors, filter networks, memory chips, or CPU chips onthe electronic module.

In still a further embodiment, the fast response time/small areathin-film thermoelectric cooling devices of the present invention can beused as identification tags for military personnel, military systems,and even commercial systems that are scanned by IR-imaging devices. Thefast response time/small area cooling devices can be arranged in aparticular order (as shown in FIG. 2) to produce fast response timeIR-tags. These IR-tags can be made to be powered only when a signal isreceived. These tags, which are based on localized hot or cold spots (asshown in FIG. 2) are, according to the present invention, amenable fordigitizing, encryption, and safe electronic transmission.

In another embodiment of the present invention, the fast-responsethermoelectric devices of the present invention are utilized inapplications for cell and molecular engineering. As such, thethermoelectric devices of the present invention provide precisetemperature control in probes and prosthetics used for microsurgery andbio-tissues probes. Specific designs to implement spot cooling orheating towards cell and molecular levels, with respect to theirdimensions and control, are shown for exemplary purposes below. Inaddition, specific application examples of the present invention areillustrated.

FIG. 11 is a schematic depiction of a thermoelectric probe 1102 of thepresent invention locally contacting a single cell 1104 of a specimen1106. Shown in FIG. 11 is an example of a cell about 50 μm in size. Theability to obtain spot cooling or heating, at flux levels in a preferredrange of 0.1 to 2000 W/cm² enabled by the present invention, can be usedto keep certain regions such for example the nucleus of the cell “cool”or “hot”, while engineering of other cell areas. Similarly, the otherparts of the cell can be kept cool or hot when the chemistry of thenucleus is manipulated with a hypodermic needle.

A thermoelectric module 1200 of the present invention thermally contactsspecific spots of the cell nucleus using for example a spring coil as acantilever, and the cooling/heating module cools or heats those specificspots of the cell. FIG. 12 is a schematic of a nano-scale thermaltransducer 1202 of the present invention employing a cantilever 1204contacting a single cell 1104. With the cantilever set up, a tip 1206approaching very small dimensions in the range of nanometers is a highlyflexible stylus exerting a lower downward force on delicate cell parts,resulting in less distortion and cell damage. A tube 1208 can provideconstituents to the cell 1106 to induce chemical or biological reactionswith the specimen 1106.

The cantilever of the present invention is similar to arrangements knownin the art for atomic force microscopy (AFM). The cantilevers of thepresent invention have spring constants of about 0.1 N/m, lower than aspring constant of 1 N/m. The integration of a thermoelectriccooling/heating device or module with a cantilever, especially thecantilevers similar to those used in AFM, provides according to thepresent invention for “nanometer-size temperature control” ofbio-tissues, cells, and perhaps other atomic-scale structures in nanotechnology such as for example nano-self-assembly.

The resonant frequency of a spring is given by: 1 F r e q u e n c y=12 KM,

where K is the spring constant and M is the mass of the spring.

Thus in contrast to AFM images, where low mass is also required (inaddition to low spring constant) to keep the resonant frequency high forhigh speed imaging, in nano-thermal transducers (or probes) of thepresent invention, a higher mass spring may be tolerable,- if not usedin a scanning mode.

In addition to spot cooling or heating of certain intra-cell features,the nano-thermal transducers of the present invention can be utilizedfor manipulation of individual DNA strains and other molecules, such aslarge molecular strands of sugar, proteins, etc. These nano-thermaltransducers can control reaction chemistries and hence biologicalprocesses of both large scale and small scale molecular structures suchas for example controlling the reactions of sugar and proteins bycontrolling the reaction chemistry of reaction mediators (such as forexample ribo-nucleic acid RNA), thereby leading to alternate approachesto genetic engineering.

The present invention also permits the study of molecular levelcalorimetry. In this embodiment of the present invention, the heat ofthe reaction is transmitted through a nano-thermal transducer, in anadiabatic system, and applied as a thermal load onto a thermoelectric(TE) device. For a fixed current through the TE device, the extrathermal load reduces the differential temperature (ΔT) that existsacross the TE device by a certain quantity. A reduction in thedifferential temperature (ΔT) translates into a reduction in the Peltiercomponent voltage across the device.

The molecular reaction proceeds over a certain time period. The fasterthe voltage of the TE device can be measured, the more sensitive the TEdevice will be. This requires smaller thermoelectric element areasbecause, for a fixed heat flux from the reaction, more ΔT will begenerated with a smaller-size thermoelement, allowing as shown below forsensitivities approaching the heat liberated by a single molecularreaction.

FIG. 13 is a schematic diagram depicting a nano scale thermal transducerof the present invention employing a nano-scale cantilever 1302contacting specific spots of large molecular structures such as ahybridized DNA pair 1304. Materials needed for the nano-thermaltransducer (i.e. the cantilever) include materials with high thermalconductivity and a low thermal emissivity; perhaps diamond-likematerials can be considered as well. For example, thermal conductivitiesin the range of 0.75 to 20 W/cm-K, and emissivities<0.3 are preferred inthe nano scale thermal transducers.

The spring constant is a function of frequency response required. Forexample, for molecular calorimetry with high spatial resolution as wella scanning mode calorimeter, low spring constant materials in additionto low density materials are utilized. For example, low densitymaterials (i.e. less than 3.0 gm/cm³) like diamond (e.g., 2.25 g/cm³) oraluminum (e.g., 2.7 g/cm³) are preferred for the present invention.

An example of nano-scale thermal control, in the attachment of amolecular fragment, at the tip of the hybridized DNA pair is shownschematically in FIG. 14 below. FIG. 14 is a schematic depicting anapparatus of the present invention for detecting the heat released froma small-scale region. The apparatus is similar to the apparatus in FIG.13, but includes a constant current power supply configured to deliver aconstant current to the thermoelectric module 1200. The sample orspecimen depicted in FIG. 14 is an organic, biological sample. However,the present invention is applicable to calorimetric determination ofheat released from inorganic samples as well as other devices thatlocally generate or dissipate heat.

The ability to control temperature at a nanoscale or molecular levelusing a combination of high-power density (or high power flux) thin-filmthermoelectric devices (as a heat pump) and AFM tip-like nanothermaltransducers enables, according to the present invention, the measurementof heat of reactions at the nanoscale or molecular level or smallgeometries (volume).

A total voltage VT across the thermoelectric device of FIG. 14 is givenby:

-   -   -   V_(T) is approximately equal to V_(R)+V_(O),

where V_(T) is the total voltage measured, V_(R) is the ohmic componentand V_(O) is the Peltier component.

-   -   Also, V_(T) is approximately equal to IR+α_(eff)ΔT,

where R is the “Ohmic” resistance of the thermoelectric module, I is aconstant current supplied through the thermoelectric device, α_(eff) isthe effective Seebeck coefficient of the thermoelectric module. Forexample, a module including m ‘p’ elements and including m ‘n’ elements,each with an α_(p) and an α_(n) respectively, will have:α_(eff) ≅m(α_(p)+α_(n)).

-   -   Combining these equations,        (V _(T) ˜IR)=α _(eff) ΔT=V _(O)

Thus, from the above equation, by measuring V_(T), knowing I, knowing R,and knowing α_(eff), ΔT is derived. R and α_(eff) of the thermoelectricmodule can be measured independently by standard techniques tocompensate for temperature variations in the known values.Thus, ΔT=(V _(T) ˜IR)/α_(eff).   (5)

From energy balance considerations, the heat flow Q is given by:Q=πI−1/2I ² R−KΔT,   (6)

where π is the Peltier coefficient of the module and K is the thermalconductance of the module, given by k (a/l)_(eff) with k being thethermal conductivity and (a/l)_(eff) being the effective aspect ratio ofthe width a to the length 1 of the thermoelectric device. From equations(5) and (6), knowing k and by measuring ΔT (and hence V_(T)), Q can alsobe derived.

Thus, Q can be the heat released per unit time from the reaction zone asshown in FIG. 14. Note that there are always heat losses. Furthermore,according to the present invention, differential calorimetry can be usedto derive Q.

Assume a first steady state condition, with a detectable heat load onthe cantilever probe from a background Q₁ heat flux:ΔT ₁=(V _(T1) −-IR)/α_(eff)Q ₁ =πI−1/2I ²R−KΔT₁

Assume a steady state heat load plus heat of reaction per unit time:ΔT ₂=(V _(T) ₂ −IR)/α_(eff).Q ₂ =πI−1/2I ² R−KΔT ₂

By measuring V_(T1) and V_(T2), for a specific current I and assuming π,k, α_(eff), R do not change significantly with small temperaturechanges, the heat of reaction is derived as follows:

Assuming the reaction is exothermic, and adiabatic condition, all theheat will be released at the nano-thermal transducer. Thus, for aconstant current I through the thermoelectric module, AT across themodule should decrease with an external heat load. Thus,ΔT1−ΔT2≅{(V _(T1) −IR)/Δ_(eff)]}−{(V _(T2) −IR)/α_(eff)}=(V _(T1) −-V_(T2))/α_(eff)

Q2−Q, defined as the heat of reaction ‘Q₀’ is:≅KΔT₂+KΔT₁≅K (ΔT₁−KΔT₂)≅K (V_(T1)−V_(T2))/α_(eff)

Therefore, Q₀, the heat of an exothermic reactor produced at A, measuredby a differential voltage at the thermoelectric module measured in Wattsor Joule/sec is K (V_(T1)−V_(T2))/α_(eff).

A smaller K, a larger α_(eff), and a smaller V_(T1)−V_(T2) allows themeasured Q₀ to be smaller; i.e., the smaller K, the larger the α_(eff),and the smaller the [V_(T1)−-V_(T2)] the more precisely Q₀ can bemeasured.

For example, to measure the standard “heat of reaction” in Joules orcalories, one must integrate as a function of time.

J_(o)=Energy released in the reaction=the integral from t=0 to t=∝ofQo·dt

Typically, a reaction persisting over three to five times constants(t_(R)) can produce a change of V_(T) during that period.

Thus, J_(o) the integral from t=0 to t=5tr of Qo·dt

The fast time response of the thin-film thermoelectric device of thepresent invention allows an accurate determination of Jo, the total heatof reaction. Also a fast time response of the thin-film module allowsthe thermoelectric device of the present invention to study a timedependent response of reactions.

If k is the thermal conductivity, and is, for example, 10 mW/cm-K:a/1=2*10⁻³,

assuming 5 μm thick film and area of device as 10 μm*10 μm

α_(eff)=500 μV/K for 1 p and 1 n element,

assuming an accuracy of ΔV_(T)=1 μV; the accuracy of Q₀ is 4*10⁻⁸W. For3t_(R)≅50 μsec, then an estimate of J_(o) is 100*10⁻⁴ Joules or about 1pJ. Note that more p and n elements can increase the α_(eff) andtherefore increase the sensitivity of the measured Q_(o).

For a 1 μm*1 μm thermoelectric element, an accuracy of ΔV_(T) of 1 nV,and advanced noise-reduction techniques, and digital-signal processing,according to the present invention, an estimate a lower limit of ameasurable Jo is 1*10⁻¹⁷ Joules or 1/100^(th) of a femtojoule.

In comparison to the heat released by each molecule during a reaction:Assume a heat of reaction=150 Kcal/mole.=150*1000* 4.18 Joules/moleJ _(molecule)≅1*10⁻¹⁸ Joules/molecule

Thus, one anticipates a lower limit of the measured heat of reactionconstitutes a reaction of only about 10 molecules from the fact that Jois 1*10⁻¹⁷ Joules.

Further, a 0.5 μm*0.5 μm thermoelement able to measure 0.1 nV can reduce3t_(R) to about 30 μsec. Consequently,Jo_(easuale)≅1*10⁻¹⁷* [(1 μm*1 μm)/(0.5 μm*0.5 μm)]⁻¹*(0.1nV/1nV)*(30μsec/50 μsec)≅1.5*10⁻¹⁹ Joules

Thus, with such a small scale thermolement, the sensitivity would easilyallow for the measuring the heat flux generated by the reaction ofapproximately 1 molecule, assuming a 150 kcal/mole reaction or perhapsas low as 22.5 Kcal/mole. Even lower heat of reactions of each moleculeare perhaps measurable with larger α_(eff) and/or larger number ofthermoelectric elements and/or better sensitive set-up.

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described herein.

1. A thermoelectric cooling and heating device comprising: a substrate;a plurality of thermoelectric elements arranged on one side of thesubstrate and configured to perform at least one of selective heatingand cooling, each thermoelectric element including, a thermoelectricmaterial, a Peltier contact contacting the thermoelectric material andconfigured to form under electrical current flow at least one of aheated junction and a cooled junction, and electrodes configured toprovide current through the thermoelectric material and the Peltiercontact; and a receptacle thermally contacting the thermoelectricelements and including an array of patches configured to receive abiological material.
 2. The device of claim 1, wherein the patches ofthe receptacle are aligned with the thermoelectric elements. 3.(canceled)
 4. The device of claim 1, wherein the biological materialincludes DNA material for genomics analysis.
 5. The device of claim 1,wherein the biological material includes proteins for proteomicsanalysis.
 6. The device of claim 1, wherein the thermoelectric elementsare configured to at least one of heat and cool the biological material.7. The device of claim 6, wherein the patches are configured to receiveas the biological material single stranded DNA and the thermoelementsare configured to control the temperature of the single stranded DNA forpolymorphism conformation.
 8. The device of claim 6, wherein thethermoelectric elements are configured to at least one of heat and coolDNA double-helix material to form single-stranded DNA material.
 9. Thedevice of claim 6, wherein the thermoelectric elements are configured toprovide localized thermo-genetic switches to switch at least one of DNAchemistry, DNA-RNA chemistry, protein synthesis, cross conversiondominant genes to recessive genes, and production of antibodies.
 10. Thedevice of claim 6, wherein the patches are configured to receive as theDNA material single stranded DNA and the thermoelements are configuredto control the temperature of the single stranded DNA for polymorphismconformation.
 11. The device of claim 6, wherein the thermoelectricelements are configured to have a thermal response time less than 1.0ms.
 12. The device of claim 11, wherein the thermoelectric elements areconfigured to heat shock biological material including at least one ofDNA material, proteins, and protein-related DNA. 13-18. (canceled)
 19. Athermoelectric cooling and heating device comprising: a substrate; aplurality of thermoelectric elements arranged on one side of thesubstrate and configured to perform at least one of selective heatingand cooling, each thermoelectric element including, a thermoelectricmaterial, a Peltier contact contacting the thermoelectric material andconfigured to form under electrical current flow at least one of aheated junction and a cooled junction, and electrodes configured toprovide current through the thermoelectric material and the Peltiercontact; and a microsurgical tool thermally contacting thethermoelectric elements and configured to control the temperature ofbio-tissues in contact with the microsurgical tool.
 20. A thermoelectriccooling and heating device comprising: a substrate; a plurality ofthermoelectric elements arranged on one side of the substrate andconfigured to perform at least one of selective heating and cooling,each thermoelectric element including, a thermoelectric material, aPeltier contact contacting the thermoelectric material and configured toform under electrical current flow at least one of a heated junction anda cooled junction, and electrodes configured to provide current throughthe thermoelectric material and the Peltier contact; and a thermo-opticphase shifter in thermal contact with the plurality of thermoelectricelements and configured to vary an index of refraction of an opticalmedium via temperature variations.
 21. The device of claim 20, whereinthe thermoelectric elements are configured to heat the thermo-opticphase shifter.
 22. The device of claim 20, wherein the thermoelectricelements are configured to cool the thermo-optic phase shifter. 23.(canceled)
 24. The device of claim 23, wherein the thermoelectricelements are configured to have a thermal response time less than 1.0ms. 25-32. (canceled)
 33. A thermoelectric cooling and heating devicecomprising: a substrate; a plurality of thermoelectric elements arrangedon one side of the substrate and configured to perform at least one ofselective heating and cooling, each thermoelectric element including, athermoelectric material, a Peltier contact contacting the thermoelectricmaterial and configured to form under electrical current flow at leastone of a heated junction and a cooled junction, and electrodesconfigured to provide current through the thermoelectric material andthe Peltier contact; and an integrated module including at least oneelectronic component in thermal contact with the plurality ofthermoelectric elements and configured to control a temperature of theat least one electronic component of the integrated module.
 34. Thedevice of claim 33, wherein the thermoelectric elements are configuredto selectively heat the at least one electronic component.
 35. Thedevice of claim 33, wherein the thermoelectric elements are configuredto selectively cool the at least one electronic component. 36-38.(canceled)
 39. The device of claim 33, wherein the integrated modulecomprises an optoelectronics module.
 40. The device of claim 39, whereinthe optoelectronics module includes at least one of a bias circuit, alaser driver, a monitor diode, a VCSEL array, an out-going opticalconnector, an in-coming optical connector, a photodetector, apre-amplification circuit, and a post-amplification circuit.
 41. Thedevice of claim 33, wherein the integrated module comprises an infraredimaging array.
 42. A thermoelectric cooling and heating devicecomprising: a substrate; a plurality of thermoelectric elements arrangedon one side of the substrate and configured to perform at least one ofselective heating and cooling, each thermoelectric element including, athermoelectric material, a Peltier contact contacting the thermoelectricmaterial and configured to form under electrical current flow at leastone of a heated junction and a cooled junction, and electrodesconfigured to provide current through the thermoelectric material andthe Peltier contact; and a switching optical network including opticalswitches in thermal contact with the plurality of thermoelectricelements and configured to control a temperature of the optical switchesin the switching optical network.
 43. The device of claim 42, whereinthe optical switches comprise electroholographic optical switches. 44.(canceled)
 45. The device of claim 42, wherein the optical switchescomprise thermocapillary switches.
 46. The device of claim 45, whereinthe optical switches comprise bubblejet switches.
 47. A thermoelectriccooling and heating device comprising: a substrate; a plurality ofthermoelectric elements arranged on one side of the substrate andconfigured to perform at least one of selective heating and cooling,each thermoelectric element including, a thermoelectric material, aPeltier contact contacting the thermoelectric material and configured toform under electrical current flow at least one of a heated junction anda cooled junction, and electrodes configured to provide current throughthe thermoelectric material and the Peltier contact; and a cellularcommunications network including micro-strip delay lines in thermalcontact with the plurality of thermoelectric elements and configured tocontrol a temperature of the micro-strip delay lines in the cellularcommunications network. 48-55. (canceled)
 56. A method for hybridizingDNA, comprising: depositing a first set of DNA strands across at least apart of a DNA array; cooling selected sites on the DNA array to attachthe first set of DNA strands onto the selected sites; heating theselected sites to unravel the attached strands of DNA and to detachstrands of DNA which are not cross-linked to the selected sites; andhybridizing the attached strands of DNA with a second set of DNAstrands.
 57. The method of claim 56, further comprising: exposing,between the steps of heating and cooling, attached DNA strands to UVlight to promote cross-linking to the selected sites.
 58. The method ofclaim 56, wherein the steps of cooling and heating comprises:controlling a temperature at the selected sites with a thermoelectriccooler including a plurality of thermoelectric elements arranged on oneside of a substrate and configured to perform at least one of selectedheating and cooling.
 59. The method of claim 58, wherein the step ofcontrolling further comprises: biasing selectively electrodes of each ofthe thermoelectric elements in at least one of a first direction to forma cooled junction and a second direction to form a heated junction. 60.The method of claim 56, wherein the step of cooling comprises: attachingthe first set of DNA strands utilizing at least one of charge-bondingand electrovalent bonding.
 61. The method of claim 60, wherein the stepof attaching further comprises: providing, prior to the step of cooling,lysine on the array, and cross-linking the first set of DNA strands tothe lysine with UV light exposure.
 62. The method of claim 56, furthercomprising: biasing the selected elements to the DNA at the selectedsites.
 63. A method for controlling temperature during electrophoresisof a biological material onto an array, comprising: depositingelectrophoretically biological material across at least a part of thearray; cooling selected sites on the array during the electrophoresis toattach a first set of biological material onto the selected sites; andheating the selected sites to detach biological material which is notcross-linked to the selected sites.
 64. The method of claim 63, furthercomprising: exposing, between the steps of heating and cooling, attachedbiological material to UV light to promote cross-linking to the selectedsites.
 65. The method of claim 63, wherein the steps of cooling andheating comprises: controlling a temperature at the selected sites witha thermoelectric cooler including a plurality of thermoelectric elementsarranged on one side of a substrate and configured to perform at leastone of selected heating and cooling.
 66. The method of claim 65, whereinthe step of controlling further comprises: biasing selectivelyelectrodes of each of the thermoelectric elements in at least one of afirst direction to form a cooled junction and a second direction to forma heated junction.
 67. The method of claim 63, wherein the step ofcooling includes the step of: attaching as the biological material atleast a first set of DNA strands and a first set of proteins.
 68. Themethod of claim 63, wherein the step of cooling comprises: attaching thebiological material utilizing at least one of charge-bonding andelectrovalent bonding.
 69. The method of claim 68, wherein the step ofattaching further comprises: providing, prior to the step of cooling,lysine on the array; and cross-linking the biological material to thelysine with UV light exposure.
 70. The method of claim 63, furthercomprising: biasing the selected elements to pool the biologicalmaterial at the selected sites. 71-76. (canceled)
 77. A method forproducing an infrared image, comprising: providing an array ofthermoelectric elements; and controlling a temperature at selected siteson the array of thermoelectric elements.
 78. The method of claim 77,wherein the step of controlling a temperature comprises: controlling aplurality of said thermoelectric elements arranged on one side of asubstrate and configured to perform at least one of selected heating andcooling.
 79. The method of claim 78, wherein the step of controllingfurther comprises: biasing selectively electrodes of each of thethermoelectric elements in at least one of a first direction to form acooled junction and a second direction to form a heated junction. 80-82.(canceled)
 83. A method for improving cellular communications,comprising: providing an array of thermoelectric elements thermallyconnected to a micro-strip delay line; and controlling a temperature ofthe micro-strip delay line in a cellular communications system.
 84. Themethod of claim 83, wherein the step of controlling a temperaturecomprises: controlling the temperature with a thermoelectric coolerincluding a plurality of thermoelectric elements arranged on one side ofa substrate and configured to perform at least one of selected heatingand cooling.
 85. The method of claim 84, wherein the step of controllingfurther comprises: biasing selectively electrodes of each of thethermoelectric elements in at least one of a first direction to form acooled junction and a second direction to form a heated junction. 86-90.(canceled)
 91. A system for hybridizing DNA material, comprising: adepositing device configured to deposit a first set of DNA strandsacross at least a part of a DNA array; means for cooling selected siteson the DNA array to attach the first set of DNA strands onto theselected sites; means for heating the selected sites to unravel theattached strands of DNA and to detach strands of DNA which are notcross-linked to the selected sites; and means for hybridizing theattached strands of DNA with a second set of DNA strands.
 92. The systemof claim 91, wherein the means for cooling and the means for heatingcomprise: a thermoelectric cooler including a plurality ofthermoelectric elements configured to perform at least one of selectedheating and cooling of the array; and a controlling device configured tocontrol a temperature at the selected sites with a thermoelectriccooler. 93-99. (canceled)
 100. A system for producing an infrared image,comprising: an array of thermoelectric elements, and a controllingdevice configured to control a temperature at selected sites on thearray of thermoelectric elements.
 101. The system of claim 100, whereinthe controlling device comprises: a thermoelectric cooler including aplurality of thermoelectric elements thermally in contact with theselected sites and configured to perform at least one of selectedheating and cooling one side of the array. 102-103. (canceled)
 104. Asystem for improving cellular communications, comprising: a controllingdevice configured to control a temperature of at least one micro-stripdelay line in a cellular communications system.
 105. The system of claim104, wherein the cellular communication system is spread spectrumsystem.
 106. The system of claim 104, wherein the controlling devicecomprises: a thermoelectric cooler including a plurality ofthermoelectric elements thermally in contact with the at least onemicro-strip delay line and configured to perform at least one ofselected heating and cooling of the at least one micro-strip delay line.107-131. (canceled)